title: An IKKα-E2F1-BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence.
abstract: Androgen-deprived prostate cancer (PCa) is infiltrated by B lymphocytes that produce cytokines that activate IκB kinase α (IKKα) to accelerate the emergence of castration-resistant tumors. We now demonstrate that infiltrating B lymphocytes and IKKα are also required for androgen-dependent expansion of epithelial progenitors responsible for prostate regeneration. In these cells and in PCa cells, IKKα phosphorylates transcription factor E2F1 on a site that promotes its nuclear translocation, association with the coactivator CBP, and recruitment to critical genomic targets that include Bmi1, a key regulator of normal and cancerous prostate stem cell renewal. The IKKα-BMI1 pathway is also activated in human PCa.
authors.affiliation: Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology.
authors.forename: Massimo
authors.initials: M
authors.lastname: Ammirante
authors.forename: Ali I
authors.initials: AI
authors.lastname: Kuraishy
authors.forename: Shabnam
authors.initials: S
authors.lastname: Shalapour
authors.forename: Amy
authors.initials: A
authors.lastname: Strasner
authors.forename: Claudia
authors.initials: C
authors.lastname: Ramirez-Sanchez
authors.forename: Weizhou
authors.initials: W
authors.lastname: Zhang
authors.forename: Ahmed
authors.initials: A
authors.lastname: Shabaik
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009364:Neoplasm Recurrence, Local / Q000503:physiopathology; D009919:Orchiectomy; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D011467:Prostate / Q000187:drug effects / Q000503:physiopathology*; D011471:Prostatic Neoplasms / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration
chemical_list: D000728:Androgens; C489421:Bmi1 protein, mouse; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D011518:Proto-Oncogene Proteins; D063150:Polycomb Repressive Complex 1; D051550:I-kappa B Kinase
keywords: B cells; prostate; regeneration